College student-athletes are at increased risk of heavy alcohol use, smokeless tobacco use, and the use of performance enhancing substances as compared to non-athlete college students. Despite recent research underscoring the need for athlete-tailored interventions, there are no evidence-based options for the prevention of substance use among college student-athletes that take into account their unique patterns and motivations for use. This void leaves colleges with few easy-to-use, effective, and economical options for meeting the needs of their student-athletes and the minimum drug education requirements set by their governing organizations. The broad aim of the proposed study is to use the innovative Multiphase Optimization Strategy (MOST; Collins et al., 2005, 2007) to develop a highly effective Internet-delivered program (myPlaybook) for the prevention of substance use among college student-athletes. The MOST approach is a systematic method for making decisions about program development and adaptation that are based on the performance of individual program components. The five core lessons of myPlaybook will undergo two rounds of randomized experimentation and targeted revision. At the conclusion of the second round, the newly optimized version of myPlaybook will be assembled and evaluated in large-scale Randomized Controlled Trial (RCT). This beta version of myPlaybook will be compared to an Internet-based college alcohol intervention with proven effectiveness with general college students (College Alc; Bersamin et al., 2007; Paschall & Antin, 2008; Paschall et al., 2006). This approach will allow us to 1) develop an intervention that is optimized for considerable impact on substance use outcomes and 2) demonstrate the need for interventions specifically adapted for college student-athletes. The proposed research will be among the first demonstrations of the MOST approach for building and evaluating behavioral interventions with greatly enhanced public health impact.